Comparative genomics is a powerful tool for uncovering patterns of mutations within genes targeted in human health concerns. To examine structure and function, we sequence targeted genes across multiple species to identify the pattern and rate of substitutions. This report summarizes our completion of projects, current ongoing research, and initiation of new advances with bioinformatic tools used to investigate gene function. In 2005-2006, we have completed another manuscript focused on the critical male-determining gene, sex determining region gene (SRY) essential to male fertility in both human and cat. SRY, and adjacent noncdoing regions, were sequenced in 36 species of cat. This manuscript is currently submitted and in review. The results show adaptive evolution taking place within SRY and changes within the protein that are considered benign compared with those that trigger deleterious developmental changes in male reproductive organs. Our ongoing projects include investigating the theory that genes on the X and Y chromosome evolve in very different ways from those on autosomes. Our data is based on nearly 24 kb from 37 species of cat. We are comparing rates of genetic change between protein-coding and noncoding regions between the X-chromosome, Y-chromosome and autosomes. This will give us a broad depiction of genome evolution that can assist in the study of human disease. In an ongoing initiative, we are using newly published whole genome sequence of dog and cat with advanced bioinformatic tools to determine gene content and order of the cat sex chromosomes. The project is focused on the development and implementation of multiple bioinformatic methods to efficiently identify genes, map their position on the cat X and Y chromosomes, and investigate their function. By comparing cat with dog, mouse and human, new insights onto the evolution, structure and function of genes in the sex chromosome are possible. Assessment of patterns of change in genes linked with human disease, including cancer, can be accomplished by comparative genomics across species.